PFKP alleviates glucose starvation-induced metabolic stress in lung cancer cells via AMPK-ACC2 dependent fatty acid oxidation.
Journal
Cell discovery
ISSN: 2056-5968
Titre abrégé: Cell Discov
Pays: England
ID NLM: 101661034
Informations de publication
Date de publication:
31 May 2022
31 May 2022
Historique:
received:
30
07
2021
accepted:
10
03
2022
entrez:
31
5
2022
pubmed:
1
6
2022
medline:
1
6
2022
Statut:
epublish
Résumé
Cancer cells adopt metabolic reprogramming to promote cell survival under metabolic stress. A key regulator of cell metabolism is AMP-activated protein kinase (AMPK) which promotes catabolism while suppresses anabolism. However, the underlying mechanism of AMPK in handling metabolic stress in cancer remains to be fully understood. In this study, by performing a proteomics screening of AMPK-interacting proteins in non-small-cell lung cancer (NSCLC) cells, we discovered the platelet isoform of phosphofructokinase 1 (PFKP), a rate-limiting enzyme in glycolysis. Moreover, PFKP was found to be highly expressed in NSCLC patients associated with poor survival. We demonstrated that the interaction of PFKP and AMPK was greatly enhanced upon glucose starvation, a process regulated by PFKP-associated metabolites. Notably, the PFKP-AMPK interaction promoted mitochondrial recruitment of AMPK which subsequently phosphorylated acetyl-CoA carboxylase 2 (ACC2) to enhance long-chain fatty acid oxidation, a process helping maintenance of the energy and redox homeostasis and eventually promoting cancer cell survival under glucose starvation. Collectively, we revealed a critical non-glycolysis-related function of PFKP in regulating long-chain fatty acid oxidation via AMPK to alleviate glucose starvation-induced metabolic stress in NSCLC cells.
Identifiants
pubmed: 35641476
doi: 10.1038/s41421-022-00406-1
pii: 10.1038/s41421-022-00406-1
pmc: PMC9156709
doi:
Types de publication
Journal Article
Langues
eng
Pagination
52Subventions
Organisme : Universidade de Macau (University of Macau)
ID : SRG2020-00002-FHS
Organisme : Universidade de Macau (University of Macau)
ID : CPG2020-00029-FHS
Informations de copyright
© 2022. The Author(s).
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